Stenosis is a narrowing or constriction of a duct or canal. A variety of disease processes, such as atherosclerotic lesions, immunological reactions, congential abnormalities, and the like, can lead to stenosis of arteries or ducts. In the case of stenosis of a coronary artery, this typically leads to myocardial ischema. Percutaneous transluminal coronary angioplasty (PTCA), the insertion and inflation of a balloon catheter into a stenotic vessel to affect its repair is widely accepted as an option in the treatment of obstructive coronary artery disease. In general, PTCA is used to increase the lumen diameter of a coronary artery partially or totally obstructed by a build-up of cholesterol fats or atherosclerotic plaque. Typically a first guidewire of about 0.038 inches in diameter is steered through the vascular system to the site of therapy. A guiding catheter, for example, can then be advanced over the first guidewire to a point just proximal of the stenosis. The first guidewire is then removed. A balloon catheter on a smaller 0.014 inch diameter second guidewire is advanced within the guiding catheter to a point just proximal of the stenosis. The second guidewire is advanced into the stenosis, followed by the balloon on the distal end of the catheter. The balloon is inflated causing the site of the stenosis to widen. The dilatation of the occlusion, however, can form flaps, fissures and dissections which threaten reclosure of the dilated vessel or even perforations in the vessel wall.
Other vascular invasive therapies include atherectomy (mechanical systems to remove plaque residing inside an artery), laser ablative therapy and the like. While the stenosis or occlusion is greatly reduced using these therapies, including PTCA, many patients experience a reoccurrence of the stenosis over a relatively short period. Restenosis, defined angiograhpically, is the recurrence of a 50% or greater narrowing of a luminal diameter at the site of a prior coronary artery disease therapy, such as a balloon dilatation in the case of PTCA therapy. Additionally, researchers have found that angioplasty or placement of a stent in the area of the stenosis irritates the blood vessel causing rapid reproduction of the inner layer of blood vessel cells and restenosis through a mechanism called hyperplasia. Restenosis is a major problem which limits the long-term efficacy of invasive coronary disease therapies. In particular, an intra-luminal component of restenosis develops near the end of the healing process initiated by vascular injury, which then contributes to the narrowing of the luminal diameter. This phenomenon is sometimes referred to as "intimal hyperplasia." In some instances, restenosis develops so rapidly that it may be considered a form of accelerated atherosclerosis induced by injury. Additionally, the rapid onset of restenosis is compounded by the lack of predictability to determine which patients, vessels, or lesions will undergo restenosis.
Although the mechanism of restenosis is not fully understood, clinical evidence suggests that restenosis results from a migration and rapid proliferation of a subset of predominately medially derived smooth muscle cells which is apparently induced by the injury caused by the invasive therapy. Such injury, for example, is caused by the angioplasty procedure when the balloon catheter is inflated and exerts pressure against the artery wall, resulting in media tearing. It is known that smooth muscle cells proliferate in response to mechanical stretch and stimulation by a variety of growth factors. It is believed that such proliferation stops one to two months after the initial invasive therapy procedure but that these cells continue to express an extracellular matrix of collagen, elastin and proteoglycans. Additionally, animal studies have shown that after balloon injury, denudation of endothelial cells occurs, followed by platelet adhesion and aggregation, and the release of platelet-derived growth factor (PDGF) as well as other growth factors. As mentioned above, this mass of tissue contributes in the re-narrowing of the vascular lumen in patients who have restenosis. It is believed that a variety of biologic factors are involved in restenosis, such as the extent of the injury, platelets, inflammatory cells, growth factors, cytokines, endothelial cells, smooth muscle cells, and extracellular matrix production, to name a few.
It has been found that irradiating the blood vessel walls at the point of the stenosis will reduce or prevent hyperplasia Precise control over the amount of radiation is important, since insufficient radiation will not prevent hyperplasia and excessive radiation can damage the blood vessel. For other diagnostic or treatment purposes, it is also often desirable to introduce a small radiation source into a body vessel such as a coronary artery. Simply inserting a wire with a source secured in the wire at or near the distal end is effective in some cases. However, the wire will tend to lie along one side of the vessel, so that the near side receives significantly more radiation than the opposite, distant side. The near side could receive excessive, damaging, radiation exposure before the opposite side received the desired dose Such a non-centering, wire-carried, radiation source is shown by Dake et al. in U.S. Pat. No. 5,199,939 and Bradshaw in U.S. Pat. No. 5,643,171.
Zoumboulis, in U.S. Pat. No. 3,324,847, describes a catheter having a spherical inflatable chamber adjacent the catheter distal end. A fluid containing a radioactive material such as radioactive iodine is pumped into the chamber, inflating the chamber and treating the vessel walls with ionizing radiation. The chamber will stop blood flow, so it can be inflated for only a short period. Further, precisely controlling radiation exposure and fully draining the chamber to end treatment are very difficult.
A wire carrying a radioactive source could be inserted through a catheter lumen to the balloon location. The balloon would approximately center the source in the artery. However, since many guidewires extend mainly alongside the balloon catheter and balloons generally expand somewhat unevenly, the source would not be precisely centered. Further, irradiating a segment of an artery or the like generally requires some time, typically from about 3 to 45 minutes. Since a conventional angioplasty balloon substantially shuts off blood flow through the artery, treatment can be conducted for only short periods before damage from lack of blood flow becomes significant.
Liprie, in International Patent Application Publication Number W095/26851 describes a device for treating a vessel occlusion with radiation in which a ribbed balloon catheter is inserted into a body vessel and inflated to provide perfusion between the ribs and a wire carrying a radiation source is inserted into a lumen extending into the balloon area. This positions the radiation source generally near the center of the vessel. However, as disclosed, the lumen has a much greater inside diameter than the outside diameter of the source wire, so that the source will generally be off center, in contact with the lumen wall. This will result in uneven irradiation of the vessel wall on opposite sides.
Other ribbed arrangements, using a double spiral rib or circumferential ribs are disclosed by Bradshaw et al. in U.S. Pat. No. 5,643,171 for centering a treatment lumen in a body vessel. While useful, the lobes may not provide precise centering, especially if the treatment wire is not a good fit in the lumen.
Teirstein in U.S. Pat. No. 5,540,659 describes a series of centering wire loops for centering a wire-carried radiation source in a body vessel. The generally oval shape of the wire loops and the complexity of inserting and removing the loop device make this arrangement less than fully effective. Teirstein also shows in his FIGS. 5 and 6 an embodiment using flexible wires that can be expanded away from a central catheter. However, the use of a single set of wires extending from the distal to proximal ends of the treatment zone will tend to allow the catheter to tilt relative to the wires. Also this system does not allow the use of multiple sets of expansion wires that could be opened independently.
A series of approximately spherical balloons are used to center a radiation source in the arrangement of Verin et al. as disclosed in European Patent Application No. 94109858.4. Although the source is centered in the vessel, lack of perfusion of blood past the site would permit only very short treatment times.
Ciamacco, in pending patent application Ser. No. 09/067,524 (Attorney Docket No. P-7770, filed Apr. 28, 1998) describes an apparatus for delivery of radiation in vivo. A device includes a seal located proximal to a balloon through which a cavity of the balloon is inflated with a composition including a radioactive compound. The seal includes a passage therethrough which provides the only access to the balloon cavity and terminates at the proximal end of the balloon. The passage through the seal provides fluid communication with an inflation lumen within the medical device lumen, wherein a ratio of an inner diameter of the inflatable member to an inner diameter of the inflation lumen is about 0.5 or greater. In such a construction, inflation and evacuation can be accomplished without contamination of the entire medical device lumen. Thus, substantially all of the solution including the radioactive compound can be evacuated from the balloon cavity after treatment due to the positioning of the passage in the seal. However, because there is only one access to the balloon cavity, inflation of the balloon with the radioactive composition and the subsequent flushing of the balloon with a non-radioactive composition can only be accomplished though a single lumen which requires vacuum pressure to remove the compositions. This, in turn, likely increases the time and the volume of radioactive waste generated to decontaminate the device.
Inplantable devices are also known for delivery of radiation in vivo that typically are an intra-arterial stents fabricated from either a pure metal or a metal alloy which has been irradiated so that is has become radioactive. However, as with any isotopes or radioactive material, the useful life, which includes both the shelf-life and the therapeutic life, of the device is limited by the half-life of the isotope utilized. The shelf-life of any device containing a radioactive material necessarily begins upon attachment of the radioisotope to the device because the radioactive material is continuously decaying. If storage and/or shipping are required, the radioactive material continues to decay to the point where any radiation emitted from the device is negligible. Thus, implantation of the device would not be advantageous.
Thus, there is a continuing need for improved devices for carrying a radiation source to a desired in vivo site that can be easily and accurately inserted into and removed from even very small vessels and which accurately center the source in the vessel while permitting effective perfusion so that treatment can be conducted over reasonably long periods. Additionally, there is a continuing need for such a device that can be subsequently decontaminated of radioactivity relatively easily.